The outputs consist of raw and normalized peak scores (multiple normalizations) in text format and scaled bigWig coverage tracks that are directly accessible to data visualization programs. BAMScale also includes a visualization module facilitating direct, on-demand quantitative peak comparisons that can be used by experimentalists. Our tool can effectively analyze large sequencing datasets (~?100&nbsp;Gb size) in minutes, outperforming currently available tools. CONCLUSIONS BAMscale accurately quantifies and normalizes identified peaks directly from BAM files, and creates coverage tracks for visualization in genome browsers. BAMScale can be implemented for a wide set of methods for calculating coverage tracks, including ChIP-seq and ATAC-seq, as well as methods that currently require specialized, separate tools for analyses, such as splice-aware RNA-seq, END-seq and OK-seq for which no dedicated software is available. BAMscale is freely available on github (https//github.com/ncbi/BAMscale).BACKGROUND Chromatin dysregulation is associated with developmental disorders and cancer. Numerous methods for measuring genome-wide chromatin accessibility have been developed in the genomic era to interrogate the function of chromatin regulators. A recent technique which has gained widespread use due to speed and low input requirements with native chromatin is the Assay for Transposase-Accessible Chromatin, or ATAC-seq. Biologists have since used this method to compare chromatin accessibility between two cellular conditions. However, approaches for calculating differential accessibility can yield conflicting results, and little emphasis is placed on choice of normalization method during differential ATAC-seq analysis, especially when global chromatin alterations might be expected. RESULTS Using an in vivo ATAC-seq data set generated in our recent report, we observed differences in chromatin accessibility patterns depending on the data normalization method used to calculate differential accessibility. This observation was further verified on published ATAC-seq data from yeast. We propose a generalized workflow for differential accessibility analysis using ATAC-seq data. https://www.selleckchem.com/products/AG-490.html We further show this workflow identifies sites of differential chromatin accessibility that correlate with gene expression and is sensitive to differential analysis using negative controls. CONCLUSIONS We argue that researchers should systematically compare multiple normalization methods before continuing with differential accessibility analysis. ATAC-seq users should be aware of the interpretations of potential bias within experimental data and the assumptions of the normalization method implemented.BACKGROUND Elderly patients represent a major fraction of non-small cell lung cancer (NSCLC) patients in routine clinical practice, but they are still underrepresented in clinical trials. In particular, data regarding efficacy and safety in frail or elderly patients with respect to immunotherapy are lacking. Importantly, immunosenescence in elderly patients might interfere with activities of immune-modulating drugs such as PD-1/PD-L1 inhibitors. Thus, there is an urgent need to assess safety and efficacy of such inhibitors in this group. METHODS/DESIGN This prospective, open label, treatment stratified, randomized phase II study will enroll 200 patients with stage IV NSCLC amenable at least to single-agent chemotherapy (CT). Eligible patients must be aged 70?years or older and/or "frail" (Charlson Comorbidity Index &gt;?1) or have a restricted performance status (Eastern Cooperative Oncology Group, ECOG &gt;?1). Patients are stratified according to modified Cancer and Age Research Group (CARG) score "fit" patients N The DURATION trial will prospectively investigate the safety and tolerability of anti-PD-L1 treatment with durvalumab after chemotherapy in elderly and frail patients and thereby provide new insights into the effect of PD-L1 blockade and the impact of immunosenescence in this cohort of patients. TRIAL REGISTRATION ClinicalTrials.gov, NCT03345810; initially registered on 17 November 2017. Eudra-CT, 2016-003963-20; initially registered on 3 January 2017.BACKGROUND The World Health Organization recommends exclusive breastfeeding for 6 months and total breastfeeding for at least 2 years. Despite this and multiple interventions promoting breastfeeding, early breastfeeding cessation remains high with little data as to the ongoing barriers contributing to early cessation. METHODS Two groups of Nicaraguan mothers in an urban hospital were approached to complete a questionnaire to determine what newborn, maternal, and socioeconomic factors contributed to early cessation of breastfeeding. Group 1 participants were mothers of newborns in the newborn units, while group 2 were mothers of children 5 years or younger in the emergency room and pediatric ward. Descriptive statistics summarized the data. Fisher's exact test evaluated factors associated with early breastfeeding cessation. RESULTS In group 1, 97 participants were enrolled with 81% of mothers planning to fulfill the guideline for exclusive breastfeeding for 6 months. In group 2, there were 139 mothers of which 58% reported they had exclusively breastfed for 6 months. Only 25 and 27% of mothers in group 1 and 2 respectively planned to breastfeed or breastfed for 2 years. In group 1, mothers reported lack of knowledge regarding breastfeeding techniques and older mothers tended to plan for early cessation of exclusive breastfeeding. In group 2, mothers reported feeling uncomfortable with breastfeeding in public or had difficulty with latching. Cessation of any breastfeeding prior to 12?months was associated with being uncomfortable breastfeeding in public and knowing the WHO guidelines. In both groups, social media represented an expanding platform for receiving breastfeeding information. CONCLUSIONS Interventions focusing on reaching younger mothers and addressing breastfeeding knowledge and techniques while leveraging the increasing influence of social media platforms may help improve compliance with breastfeeding recommendations.